Maximum Daily Dose of Nitroglycerin (Nitropatch)
The maximum recommended dose for transdermal nitroglycerin (nitropatch) is 0.8 mg per hour every 12 hours, which should be applied with a nitrate-free interval to prevent tolerance development. 1
Dosing Guidelines for Transdermal Nitroglycerin
- Transdermal nitroglycerin patches are typically dosed at 0.2 to 0.8 mg per hour every 12 hours 1
- The duration of effect is approximately 8 to 12 hours during intermittent therapy 1
- Patches should be applied with a nitrate-free interval (typically overnight) to prevent tolerance development 1, 2
Tolerance Considerations
- Tolerance to the hemodynamic effects of nitrates is dose and duration dependent, typically becoming significant after 24 hours of continuous therapy 1
- Continuous 24-hour application leads to complete tolerance development and loss of efficacy 2, 3
- Even prolonged (2-4 weeks) intravenous infusion at 300-400 mcg/min does not increase methemoglobin levels, suggesting safety at these higher doses for short-term use 1
Administration Recommendations
- Apply patches in the morning and remove at bedtime to provide a nitrate-free interval during sleep (when angina is less common) 4
- This intermittent therapy approach helps maintain nitrate sensitivity during daytime hours 2, 4
- Avoid continuous 24-hour application as studies show loss of antianginal effects after 24-48 hours of continuous use 5
Important Precautions
- Nitroglycerin is contraindicated after the use of sildenafil within the previous 24 hours or tadalafil within 48 hours due to risk of profound hypotension, MI, and even death 1
- The suitable delay before nitrate administration after vardenafil use has not been definitively determined, but blood pressure generally returns to baseline by 24 hours 1
- Nitroglycerin should be avoided in patients with systolic blood pressure less than 90 mmHg or 30 mmHg below baseline, or with marked bradycardia or tachycardia 1
Rebound Ischemia Concerns
- Some patients may experience increased ischemia during patch-off hours (rebound phenomenon) 6
- In one study, angina frequency increased during patch-off hours with transdermal nitroglycerin (1.1 ± 2.1) compared with placebo (0.7 ± 1.6) 6
- This rebound phenomenon is clinically relevant only in a minority of patients but should be monitored 2
Alternative Nitrate Formulations
- For patients with ongoing refractory ischemic symptoms, intravenous nitroglycerin may be used with a ceiling dose of 200 mcg/min commonly recommended 1
- Oral nitrates (isosorbide dinitrate 5-80 mg 2-3 times daily or isosorbide mononitrate 20 mg twice daily) are acceptable alternatives for patients requiring antianginal therapy without ongoing refractory symptoms 1